Acetone found in a human's blood, urine, and breath can be a marker for various biological processes, the most notable of which is diabetic ketoacidosis associated with insulin insufficiency. Also, acetone can also be an indicator of poor regulation of a ketogenic diet that is used to control refractory epileptic seizures.
Conventional monitoring devices for diabetic ketoacidosis and regulating ketogenic diets often rely on invasive sample collection, such as blood tests. The American Diabetes Association recommends that diabetics monitor their glucose levels several times a day. However, because of the invasive nature of conventional monitoring devices, many diabetics with type 1 (“insulin dependent”) diabetes monitor glucose levels only once a day and most diabetics with type 2 (“insulin resistant”) diabetes do not monitor glucose levels daily.
Ketone generation in the body is known to be associated with certain conditions. Referring to FIG. 1, insulin facilitates the transport of glucose into the cell to generate energy. Diabetes generally occurs when either the amount of insulin is insufficient (type 1 diabetes) or the insulin is not effective (type 2 diabetes). As a result, the blood glucose level can rise and the cells become glucose-starved. Ketogenesis in the mitochondria then converts triglycerides (fatty acids) to acetoacetate (AcAc) and energy. The AcAc interconverts with 3-hydroxybutyrate (3HB) and also undergoes spontaneous decarboxylation to form acetone (Me2O). Together these three products (AcAc, 3HB, and Me2O) are known as ketone bodies, which can partition across the cell wall and into the blood.
Of the three ketone bodies, only acetone is sufficiently volatile to partition into the alveolar air, while AcAc and 3HB remain in the blood. The partition coefficient, K, for Me.sub.2O at the blood/air interface is between 208 and 597, a factor even more favorable that that of ethanol. The ethanol partition coefficient is used in determining the blood alcohol content or blood alcohol concentration (BAC) of an individual. The acetone that partitions into the alveolar air generates the sweet smell characteristic of diabetic ketoacidosis, which is sometimes referred to as “acetone breath.”
Diabetic ketoacidosis occurs as the fatty acids are consumed and the concentration of ketone bodies rises. For normal subjects, the concentration ratio of 3HB to AcAc is about 1:1 and the total concentration of ketone bodies is below 0.5 mM. Under diabetic ketoacidotic conditions, the ratio of 3HB to AcAc increases to about 3:1, or even as high as 10:1, and the concentration of the ketone bodies drastically increases. Concentrations for the ketone bodies are listed in Table 1 for human subjects who are healthy individuals, treated diabetics, and ketoacidotic diabetics.
TABLE 1Plasma Concentrations of Ketone Bodies in Plasma (mM).KetoacidoticKetone BodyNormal SubjectTreated DiabeticDiabeticAcetone (Me2O)0.015 ± 0.0051.69 ± 0.783.26 ± 0.79Acetoacetate (AcAc)0.114 ± 0.0290.306 ± 0.05 2.84 ± 0.403-Hydroxy-butyrate0.160 ± 0.0500.810 ± 0.1718.23 ± 1.48(3HB)pH——7.29 ± 0.01
As can be seen in Table 1, the concentration of acetone in a ketoacidotic diabetic is approximately two times greater than that of a treated diabetic, and the concentration of acetone is roughly a hundred times greater in a treated diabetic than a normal subject. Also, the concentrations of AcAc and 3HB in a ketoacidotic diabetic are roughly 25 times higher and 50 times higher than that of a normal subject, respectively.
The ketone body composition illustrates that acetone measurement can be an effective marker for the onset of ketoacidosis and the ketoacidotic state. Ketoacidosis can be followed by the 3HB concentration as it tracks with the total ketone load. Breath acetone correlates with plasma 3HB over a clinically relevant range. Thus, by tracking acetone on the breath, 3HB can be reliably measured and the onset of ketoacidosis can be tracked.
Portable sensors have been developed for measuring alcohol on a human's breath. Breathalyzers determine the BAC by measuring the ethanol concentration in alveolar air that is exhaled from deep within the lungs. Because there is an equilibrium of ethanol between the blood and alveolar air, the ethanol concentration in the breath is generally proportional to the ethanol concentration in the blood.